Wound healing is a complex cascade of events that attempts to maintain homeostasis in the wounded tissue. Closing of the wound is essential to the healing process as it protects the tissue itself from infection with foreign agents, such as opportunistic bacterial pathogens. Biofilms established by these pathogens are a common cause of chronic infections that slow the process of wound healing. The bacterial biofilms themselves are challenging to eliminate with conventional antibiotics due to an extensive exopolymeric layer covering the pathogen that limits diffusion of these drugs into the biofilm. Ionic liquids, such including deep eutectic solvents (DESs), is a family of molecules with diverse chemical properties.
When considering dermal wound healing, there is a driving need for the organism to close the wound from the environment as a form of protection. If the wound does not close in a sufficient amount of time, foreign agents can enter the body and have serious pathological effects. Additionally, in a clinical environment, various devices and/or materials are implanted into the integument (skin) to treat the skin or other tissues and organs. In these cases, altering the skin environment can present significant risks to the organism (patient) for bacteria, viral, or fungal contamination of the compromised skin.
A specific patient population at significant risk for open wound contamination by biofilm formation includes unmanaged diabetic patients who develop chronic, non-healing wounds. Diabetic foot ulcers affect an estimated 1.4 million people in the U.S., resulting in enormous health care expenditures estimated at more than $176 billion per year for 2012 (Margolis et al., Incidence of diabetic foot ulcer and lower extremity amputation among Medicare beneficiaries, 2006 to 2008, Data Points Publication Series, Feb. 17, 2011; Mathieu, D. (Ed). Handbook on hyperbaric medicine (Vol. 27). New York: Springer. 2006; Menke, et al., Impaired wound healing. Clinics in dermatology, 25(1), 19-25. 2007. Washington health system: Washington hospital. (2014)). Diabetic patients who have chronic disease may experience persistent wounds for months to years. Furthermore, if healing occurs, the healed tissue has substantial scarring and the scar may fail, resulting in recurrence of the ulcer.
Chronic diabetic wounds pose different pathophysiological abnormalities that contribute to a complex wound microenvironment that varies from the “normal” wound healing cascade (Falanga, V. Wound healing and its impairment in the diabetic foot. The Lancet, 366(9498), 1736-1743. 2005). This variation leads to a loss of synchrony of events indicative of rapid healing. There is a pathogenic triad of events that are predisposed in diabetic patients consisting of neuropathy, ischemia and trauma that hinders normal healing. Each of these factors affects each other in a way that results in an impaired ability to fight infection and presents difficulties in closing chronic skin wounds.
Currently, the clinical treatment of full thickness skin wounds presents a significant challenge. Therapies for the treatment of these skin wounds include autologous tissue grafts and fat transplantation (replacing burnt or severely traumatized tissue with a patient's own skin & fat tissue—taken from a distant site), and alloplastic (synthetic) implants. However, these methods present significant problems for the patient including donor site morbidity, implant migration, rupture, volume reduction, and foreign body reaction (Sterodimas, Aris, et al. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. Journal of Plastic, Reconstructive & Aesthetic Surgery 63.11: 1886-1892, 2010; Stosich, et al. Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery. Plastic and reconstructive surgery 119.1: 71, 2007).
Furthermore, a lack of subcutaneous adipose tissue in full thickness skin wounds contributes to the aesthetically unappealing post-operative appearance (Shill K, et al. (2011) Ionic liquid pretreatment of cellulosic biomass: enzymatic hydrolysis and ionic liquid recycle. Biotechnology and bioengineering 108(3):511-520). There remains a major clinical demand for better methods of skin tissue healing of diabetic foot ulcers but also following severe burns, tumor excision, and trauma (Sterodimas, Aris, et al. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. Journal of Plastic, Reconstructive & Aesthetic Surgery 63.11: 1886-1892, 2010).
In the clinical treatment of wounds, it is well established that open skin wounds colonize with bacteria; therefore, optimized wound care targets rapid wound closure in efforts to prevent infection and possible sepsis in severe cases (Wysocki, Annette B. Evaluating and managing open skin wounds: colonization versus infection. AACN Advanced Critical Care 13.3: 382-397, 2002). Today, wound care to prevent progression from colonization to infection remains the paramount objective of health care providers. However, this progression has become progressively difficult to combat due to emergent antimicrobial resistance (Davis, S. C., et al. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair and Regeneration, 2008, 16: 23-29).